PHARMACEUTICAL COMPOSITION FOR PREVENTION AND TREATMENT FOR HEPATITIS C CONTAINING CYCLIN A2 EXPRESSION OR ACTIVITY INHIBITOR

Hepatitis C viruses (HCV) require host cell proteins for proliferation thereof. In order to verify cell factors essential to HCV proliferation, a siRNA library targeting a cell cycle was screened by using cells infected with HCV grown through cell proliferation, and a gene coding cyclin A was selected and characterized. CycA2 deregulation was associated with several types of tumors including liver cancer. The effects of CycA2 on HCV proliferation was studied by siRNA mediated knockdown assay, in vitro and in vivo protein binding assay, luciferase reporter gene assay, and immunoblotting assay. The siRNA-mediated CycA2 reduction remarkably inhibited HCV replication for both HCV sub-genomic replicon cells and cells infected with HCVcc. In addition, HCV NS5B specifically interacted with CycA2 in vivo and in vitro. The protein interaction was mediated through the cyclin box of CycA2 and the palm domain of NS5B. The R/HxL motif of the palm domain of NS5B mediates protein interaction with CycA2, and this interaction is essential in HCV replication. Further, tylophorine, which is a product of a natural plant and inhibits CycA2 activity, inhibited HCV replication. In conclusion, HCV regulates CycA2 through NS5B protein for self renewal, and tylophorine has a potential as a HCV therapeutic agent.